Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers

被引：396

作者：

Hirvonen, J. ^{[1
]}

Goodwin, R. S. ^{[2
]}

Li, C-T ^{[1
]}

Terry, G. E. ^{[1
]}

Zoghbi, S. S. ^{[1
]}

Morse, C. ^{[1
]}

Pike, V. W. ^{[1
]}

Volkow, N. D. ^{[3
]}

Huestis, M. A. ^{[2
]}

Innis, R. B. ^{[1
]}

机构：

[1] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA

[2] NIDA, Chem & Drug Metab Sect, NIH, Baltimore, MD USA

[3] NIDA, Off Director, NIH, Bethesda, MD 20892 USA

来源：

MOLECULAR PSYCHIATRY | 2012年 / 17卷 / 06期

基金：

芬兰科学院;

关键词：

addiction; cannabis; CB1; receptor; positron emission tomography; receptor imaging; BINDING; DELTA(9)-TETRAHYDROCANNABINOL; MARIJUANA; DELTA-9-TETRAHYDROCANNABINOL; ADAPTATION; DEPENDENCE; TOLERANCE; SINGLE; RADIOLIGAND; ANTAGONIST;

D O I：

10.1038/mp.2011.82

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB1 (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in human subjects who chronically smoke cannabis. Downregulation correlated with years of cannabis smoking and was selective to cortical brain regions. After similar to 4 weeks of continuously monitored abstinence from cannabis on a secure research unit, CB1 receptor density returned to normal levels. This is the first direct demonstration of cortical cannabinoid CB1 receptor downregulation as a neuroadaptation that may promote cannabis dependence in human brain. Molecular Psychiatry (2012) 17, 642-649; doi:10.1038/mp.2011.82; published online 12 July 2011

引用

页码：642 / 649

页数：8

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